Perinatal Exposure to Glyphosate and Propiconazole Impairs the Development of the Male Rat Mammary Gland.

GOMEZ AL; ALTAMIRANO GA; SCHIERANO-MAROTTI G; MUÑOZ-DE-TORO M; KASS L

Workshop; 8th Latin American Pesticide Residue Workshop; 2021

Exposure to Glyphosate (GLY)during critical developmental periods induces adverse effects on thereproductive system of male rats, and we have shown that glyphosate-basedherbicides produce endocrine-disrupting effects on the male rat mammary gland.On the other hand, propiconazole (PRO) has been shown to cause alterations insteroidogenesis and to be a hepatotoxic compound, which could alter the hepaticresponse to xenobiotics and, therefore, modify the effects induced by GLY when amixture of both agrochemicals is used. Here, our aim was to evaluate whether developmental exposure to PRO, GLY or both(PROGLY) alter mammary gland development in postpubertal male rats. Pregnantrats were orally exposed to vehicle (saline solution), 4 mg/kg/day of PRO, 4mg/kg/day of GLY, or a mixture of PRO and GLY (each 4 mg/kg/day), fromgestation day 9 until weaning. On postnatal day 60, male offspring were euthanized,and mammary gland samples were collected. Totalarea, perimeter, longitudinal growth, numberof terminal end buds and mammary developmentalscore were analyzed in mammary gland whole-mounts (WMs). Lobuloalveolar development and the presence of hyperplastic structureswere evaluated in histological sections, as well as proliferation (Ki67) andprotein expression of estrogen receptor alpha (ESR1), androgen receptor (AR)and aromatase (ARO). In addition, the mRNA expression of ARO, cyclin D1 (Ccnd1)and Wnt5a was assessed. Among the parameters evaluated in WM, only the totalarea of the mammary gland was affected in the exposed animals and it was reducedin the males exposed to GLY (Control: 492±16 mm2, GLY: 419±21 mm2,PRO: 436±17 mm2, PROGLY: 473±19 mm2; Control vs GLY p<0.05). Regarding themorphology of the mammary gland, PRO animals presented an enhancelobuloalveolar development (p<0.05), and 27% of the animals developedlobular hyperplasias, whereas no differences were observed in the percentage ofhyperplastic ducts between the experimental groups (p>0.05). In GLY males, theprotein expression of ESR1 was lower (Control: 15.3±0.72%,GLY: 11.0±0.74%, PRO: 15.5±1.4, PROGLY: 12.6±1.0%; Control vs GLY p<0.05), whereas the proteinexpression of ARO was higher compared to Control animals (Control: 0.32±0.02,GLY: 0.43±0.02, PRO: 0.30±0.04, PROGLY: 0.29±0.02, IOD values; Control vs GLY p<0.05). The proliferationindex, AR protein expression and the mRNA expression of ARO, Ccnd1 and Wnt5a weresimilar between the experimental groups (p>0.05). In summary, bothagrochemicals alter the male mammary gland development, PRO induces mammarygland lesions, whereas GLY reduces the mammary gland area. However, theseeffects are not observed when males are exposed simultaneously to a mixture of bothcompounds.